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Aims: To evaluate the effect of video information given before cardiovascular magnetic resonance imaging on patient anxiety and to compare patient experiences of cardiovascular magnetic resonance imaging versus myocardial perfusion scintigraphy. To evaluate if additional information has an impact on motion artefacts.less thanbr /greater thanBackground: Cardiovascular magnetic resonance imaging and myocardial perfusion scintigraphy are technically advanced methods for the evaluation of heart diseases. Although cardiovascular magnetic resonance imaging is considered to be painless, patients may experience anxiety due to the closed environment.less thanbr /greater thanDesign: A prospective randomized intervention study, not registered.less thanbr /greater thanMethods: The sample (n=148) consisted of 97 patients referred for cardiovascular magnetic resonance imaging, randomized to receive either video information in addition to standard text-information (CMR-video/n=49) or standard text-information alone (CMR-standard/n=48). A third group undergoing myocardial perfusion scintigraphy (n=51) was compared with the cardiovascular magnetic resonance imaging-standard group. Anxiety was evaluated before, immediately after the procedure and one week later. Five questionnaires were used: Cardiac Anxiety Questionnaire, State-Trait-Anxiety Inventory, Hospital-Anxiety and Depression-scale, MRI-Fear-Survey-Schedule and the MRI-Anxiety-Questionnaire. Motion artefacts were evaluated by three observers, blinded to the information given. Data were collected between April 2015 and April 2016. The study followed the CONSORT guidelines RESULT: The CMR-video group scored lower (better) than the cardiovascular magnetic resonance imaging-standard group in the factor Relaxation (p=0.039) but not in the factor Anxiety. Anxiety levels were lower during scintigraphic examinations compared to the CMR-standard group (pless than0.001). No difference was found regarding motion artefacts between CMR-video and CMR-standard.less thanbr /greater thanConclusion: Patient ability to relax during cardiovascular magnetic resonance imaging increased by adding video information prior the exam, which is important in relation to perceived quality in nursing. No effect was seen on motion artefacts.less thanbr /greater thanRelevance To Clinical Practice: Video information prior to examinations can be an easy and time effective method to help patients cooperate in imaging procedures.

Background To assess myocardial perfusion, steady-state free precession cardiac magnetic resonance (SSFP, CMR) was compared with gradient-echo–echo-planar imaging (GRE-EPI) using myocardial perfusion scintigraphy (MPS) as reference. Methods Cardiac magnetic resonance perfusion was recorded in 30 patients with SSFP and in another 30 patients with GRE-EPI. Timing and extent of inflow delay to the myocardium was visually assessed. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Myocardial scar was visualized with a phase-sensitive inversion recovery sequence (PSIR). All scar positive segments were considered pathologic. In MPS, stress and rest images were used as in clinical reporting. The CMR contrast wash-in slope was calculated and compared with the stress score from the MPS examination. CMR scar, CMR perfusion and MPS were assessed separately by one expert for each method who was blinded to other aspects of the study. Results Visual assessment of CMR had a sensitivity for the detection of an abnormal MPS at 78% (SSFP) versus 91% (GRE-EPI) and a specificity of 58% (SSFP) versus 84% (GRE-EPI). Kappa statistics for SSFP and MPS was 0·29, for GRE-EPI and MPS 0·72. The ANOVA of CMR perfusion slopes for all segments versus MPS score (four levels based on MPS) had correlation r = 0·64 (SSFP) and r = 0·96 (GRE-EPI). SNR was for normal segments 35·63 ± 11·80 (SSFP) and 17·98 ± 8·31 (GRE-EPI), while CNR was 28·79 ± 10·43 (SSFP) and 13·06 ± 7·61 (GRE-EPI). Conclusion GRE-EPI displayed higher agreement with the MPS results than SSFP despite significantly lower signal intensity, SNR and CNR.

Aim. To develop and validate a new instrument measuring patient anxiety during Magnetic Resonance Imaging examinations, Magnetic Resonance Imaging-Anxiety Questionnaire. Background. Questionnaires measuring patients anxiety during Magnetic Resonance Imaging examinations have been the same as used in a wide range of conditions. To learn about patients experience during examination and to evaluate interventions, a specific questionnaire measuring patient anxiety during Magnetic Resonance Imaging is needed. Design. Psychometric cross-sectional study with test-retest design. Methods. A new questionnaire, Magnetic Resonance Imaging-Anxiety Questionnaire, was designed from patient expressions of anxiety in Magnetic Resonance Imaging-scanners. The sample was recruited between October 2012-October 2014. Factor structure was evaluated with exploratory factor analysis and internal consistency with Cronbachs alpha. Criterion-related validity, known-group validity and test-retest was calculated. Results. Patients referred for Magnetic Resonance Imaging of either the spine or the heart, were invited to participate. The development and validation of Magnetic Resonance Imaging-Anxiety Questionnaire resulted in 15 items consisting of two factors. Cronbachs alpha was found to be high. Magnetic Resonance Imaging-Anxiety Questionnaire correlated higher with instruments measuring anxiety than with depression scales. Known-group validity demonstrated a higher level of anxiety for patients undergoing Magnetic Resonance Imaging scan of the heart than for those examining the spine. Test-retest reliability demonstrated acceptable level for the scale. Conclusion. Magnetic Resonance Imaging-Anxiety Questionnaire bridges a gap among existing questionnaires, making it a simple and useful tool for measuring patient anxiety during Magnetic Resonance Imaging examinations.

BACKGROUND: The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis.

RESULTS: The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure.

CONCLUSIONS: Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality.

Background: The use of a balloon expandable stent valve includes balloon predilatation of the aortic stenosis before valve deployment. The aim of the study was to see whether or not balloon predilatation is necessary in transcatheter aortic valve replacement (TAVI). Methods: Sixty consecutive TAVI patients were randomized to the standard procedure or to a protocol where balloon predilatation was omitted. Results: There were no significant differences between the groups regarding early hemodynamic results or complication rates. Conclusions: TAVI can be performed safely without balloon predilatation and with the same early results as achieved with the standard procedure including balloon predilatation. The reduction in the number of pacing periods required may be beneficial for the patient.

Background: Heart failure is a huge health problem. The possibility of long-term monitoring heart function more accurately in these patients has gained increasing interest. The primary aim of this study was to see if a wireless pressure sensor can be safely implanted to give accurate and reproducible long-term intracardiac pressure recordings. Another aim was to see if there are any adverse effects connected with the implant. A control group was included for comparison of clinical data.

Methods: Forty patients with heart failure, 31 scheduled for open heart surgery and 9 for transcatheter aortic valve replacement (TAVR) were included to test the safety and feasibility of the Titan™ pressure sensor. The patients were randomized to the implant or control group.

Findings: Initial sensor measurements showed very good correlation with reference pressure values from a fluid-filled catheter, and there was no need for calibration of the sensor. At the 6-month follow-up 11 patients had been wearing the implant for >1 year with a median time of 560 days. Ten of these had adequate sensor function. Compared to the control group there was no difference in adverse clinical events and the overall number of complications was low.

Conclusions: This first study in man on a new implantable wireless hemodynamic monitor showed favorable results regarding our primary endpoints; accuracy of recordings over time and safety profile. The technology has great potential for monitoring at home since it is easy to use in the out-patient setting.

Aims This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. Methods and results The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean +/- 1.96 SD) of 0.5 +/- 5.7 mL for LA minimum volume and -1.6 +/- 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. Conclusion The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings.

Turbulence and flow eccentricity can be measured by magnetic resonance imaging (MRI) and may play an important role in the pathogenesis of numerous cardiovascular diseases. In the present study, we propose quantitative techniques to assess turbulent kinetic energy (TKE) and flow eccentricity that could assist in the evaluation and treatment of stenotic severities. These hemodynamic parameters were studied in a pre-treated aortic coarctation (CoA) and after several virtual interventions using computational fluid dynamics (CFD), to demonstrate the effect of different dilatation options on the flow field. Patient-specific geometry and flow conditions were derived from MRI data. The unsteady pulsatile flow was resolved by large eddy simulation (LES) including non-Newtonian blood rheology. Results showed an inverse asymptotic relationship between the total amount of TKE and degree of dilatation of the stenosis, where the pre-stenotic hypoplastic segment may limit the possible improvement by treating the CoA alone. Spatiotem-poral maps of TKE and flow eccentricity could be linked to the characteristics of the post-stenotic jet, showing a versatile response between the CoA dilatations. By including these flow markers into a combined MRI-CFD intervention framework, CoA therapy has not only the possibility to produce predictions via simulation, but can also be validated pre-and immediate post treatment, as well as during follow-up studies.

Wall shear stress (WSS) disturbances are commonly expressed at sites of abnormal flow obstructions and may play an essential role in the pathogenesis of various vascular diseases. In laminar flows these disturbances have recently been assessed by the transverse wall shear stress (transWSS), which accounts for the WSS multidirectionality. Site-specific estimations of WSS disturbances in pulsatile transitional and turbulent type of flows are more challenging due to continuous and unpredictable changes in WSS behavior. In these complex flow settings, the transWSS may serve as a more comprehensive descriptor for assessing WSS disturbances of general nature compared to commonly used parameters. In this study large eddy simulations (LES) were used to investigate the transWSS properties in flows subjected to different pathological turbulent flow conditions, governed by a patient-specific model of an aortic coarctation pre and post balloon angioplasty. Results showed that regions of strong near-wall turbulence were collocated with regions of elevated transWSS and turbulent WSS, while in more transitional-like near-wall flow regions a closer resemblance was found between transWSS and low, and oscillatory WSS. Within the frame of this study, the transWSS parameter demonstrated a more multi-featured picture of WSS disturbances when exposed to different types of flow regimes, characteristics which were not depicted by the other parameters alone. (C) 2016 Published by Elsevier Ltd.

Background: Although it is well known that renal artery stenosis may cause renovascular hypertension, it is unclear how the degree of stenosis should best be measured in morphological images. The aim of this study was to determine which morphological measures from Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA) are best in predicting whether a renal artery stenosis is hemodynamically significant or not. Methods: Forty-seven patients with hypertension and a clinical suspicion of renovascular hypertension were examined with CTA, MRA, captopril-enhanced renography (CER) and captopril test (Ctest). CTA and MRA images of the renal arteries were analyzed by two readers using interactive vessel segmentation software. The measures included minimum diameter, minimum area, diameter reduction and area reduction. In addition, two radiologists visually judged the diameter reduction without automated segmentation. The results were then compared using limits of agreement and intra-class correlation, and correlated with the results from CER combined with Ctest (which were used as standard of reference) using receiver operating characteristics (ROC) analysis. Results: A total of 68 kidneys had all three investigations (CTA, MRA and CER + Ctest), where 11 kidneys (16.2 %) got a positive result on the CER + Ctest. The greatest area under ROC curve (AUROC) was found for the area reduction on MRA, with a value of 0.91 (95 % confidence interval 0.82-0.99), excluding accessory renal arteries. As comparison, the AUROC for the radiologists visual assessments on CTA and MRA were 0.90 (0.82-0.98) and 0.91 (0.83-0.99) respectively. None of the differences were statistically significant. Conclusions: No significant differences were found between the morphological measures in their ability to predict hemodynamically significant stenosis, but a tendency of MRA having higher AUROC than CTA. There was no significant difference between measurements made by the radiologists and measurements made with fuzzy connectedness segmentation. Further studies are required to definitely identify the optimal measurement approach.

In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4mL/min (standard deviation [SD] 20.2mL/min) versus 59.2mL/min (SD 17.4mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3mL/min (95% CI 11.1-25.6mL/min; p &lt; 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade 2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p=0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. A follow-up study of the SCHEDULE trial, which randomized de novo heart transplant recipients to everolimus with cyclosporine discontinuation or to standard-exposure cyclosporine, shows that measured glomerular filtration rate remains significantly higher in the everolimus group at three years posttransplant, with significantly reduced progression of allograft vasculopathy compared to cyclosporine therapy.

Objectives: Transcatheter Aortic Valve Implantation is now a well-established procedure and continuous development has improved the technique. The object of this paper is to describe the successive steps taken at our department to improve our protocol, resulting in a more effective and patient-safe procedure.

Design: An echo-guided method for aortic cusp alignment was used in 229 patients. In 139 patients pre-dilatation was excluded from the protocol. In the last 47 of the patients we exchanged the stiff guide-wire in the left ventricle with a soft wire for valve placement.

Results: There was a significant decrease in the use of contrast medium during the period with 90% of patients receiving less than 50 ml contrast and 35% no contrast at all. In more than half the patients we only used rapid pacing in association with deployment of the stent valve. We had six cases ofpericardial bleeding due to penetration of the stiff guide wire through the left ventricular (LV) wall. This complication was avoided in all subsequent patients where we exchanged the stiff catheter to a soft guidewire in the ascending aorta before introduction of the wire and stent valve into the LV.

Conclusions: We have successively modified our standard protocol for implantation of a balloon-expandable transcatheter aortic valve. This has simplified the procedure and reduced the risk for certain procedure-related complications.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

AimTo explore whether high-level endurance training in early age has an influence on the arterial wall properties in young women. MethodsForty-seven athletes (ATH) and 52 controls (CTR), all 17-25 years of age, were further divided into runners (RUN), whole-body endurance athletes (WBA), sedentary controls (SC) and normally active controls (AC). Two-dimensional ultrasound scanning of the carotid arteries was conducted to determine local common carotid artery (CCA) geometry and wall distensibility. Pulse waves were recorded with a tonometer to determine regional pulse wave velocity (PWV) and pulse pressure waveform. ResultsCarotid-radial PWV was lower in WBA than in RUN (P amp;lt; .05), indicating higher arterial distensibility along the arm. Mean arterial pressure was lower in ATH than in CTR and in RUN than in WBA (P amp;lt; .05). Synthesized aortic augmentation index (AI@75) was lower among ATH than among CTR (-12.8 1.6 vs -2.6 +/- 1.2%, P amp;lt; .001) and in WBA than in RUN (-16.4 +/- 2.5 vs -10.7 +/- 2.0%, P amp;lt; .05), suggesting a diminished return of reflection waves to the aorta during systole. Carotid-femoral PWV and intima-media thickness (IMT), lumen diameter and radial distensibility of the CCA were similar in ATH and CTR. ConclusionElastic artery distensibility and carotid artery IMT are not different in young women with extensive endurance training over several years and in those with sedentary lifestyle. On the other hand, our data suggest that long-term endurance training is associated with potentially favourable peripheral artery adaptation, especially in sports where upper body work is added. This adaptation, if persisting later in life, could contribute to lower cardiovascular risk.

Background and purpose Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R-1, transverse relaxation R-2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images. Methods In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R-1, R-2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model. Results R-1, R-2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (Pamp;lt;.0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor. Conclusion Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R-1 and R-2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.

OBJECTIVE: The indications for and the risk and benefit of concomitant surgical ablation for atrial fibrillation (AF) have not been fully delineated. Our aim was to survey whether the Cox-maze IV procedure is associated with postoperative heart failure (PHF) or other adverse short-term outcomes after mitral valve surgery (MVS).

RESULTS: The patients in the Maze group were younger, were in lower NYHA classes, had better right ventricular function and had lower pulmonary artery pressure. The Maze group had 30 min longer median cross-clamp time (CCT) and 50% had PHF compared with 33% in the No-maze group, p = 0.09. Two patients in the No-maze group died within one year of surgery. Congestive heart failure (OR 4.3 [CI 95%: 1.8-10], p < 0.0001) and CCT (OR 1.03 [CI 95%: 1.01-1.04], p = 0.001) were associated with PHF.

CONCLUSION: The current data cannot exclude that concomitant cryoablation increases the risk for PHF, possibly by increasing the cross clamp time.

Assessment of image analysis methods and computer software used in Tc-99m-MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in Tc-99m-MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo-simulated scintillation camera imaging of digital phantoms with time-varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (T-max) were reported by 21 of the 28 Swedish departments performing Tc-99m-MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The T-max estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior-posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic Tc-99m-MAG3 renography, especially for patients with impaired renal function.

Magnetic Resonance Angiography (MRA) and Phase-Contrast MRA (PC-MRA) approaches used for assessment of cardiovascular morphology typically result in data containing information from the entire cardiac cycle combined into one 2D or 3D image. Information specific to each timeframe of the cardiac cycle is, however, lost in this process. This study proposes a novel technique, called Phase-Contrast Magnetic Resonance CardioAngiography (4D PC-MRCA), that utilizes the full potential of 4D Flow CMR when generating temporally resolved PC-MRA data to improve visualization of the heart and major vessels throughout the cardiac cycle. Using non-rigid registration between the timeframes of the 4D Flow CMR acquisition, the technique concentrates information from the entire cardiac cycle into an angiographic dataset at one specific timeframe, taking movement over the cardiac cycle into account. Registration between the timeframes is used once more to generate a time-resolved angiography. The method was evaluated in ten healthy volunteers. Visual comparison of the 4D PC-MRCAs versus PC-MRAs generated from 4D Flow CMR using the traditional approach was performed by two observers using Maximum Intensity Projections (MIPs). The 4D PC-MRCAs resulted in better visibility of the main anatomical regions of the cardiovascular system, especially where cardiac or vessel motion was present. The proposed method represents an improvement over previous PC-MRA generation techniques that rely on 4D Flow CMR, as it effectively utilizes all the information available in the acquisition. The 4D PC-MRCA can be used to visualize the motion of the heart and major vessels throughout the entire cardiac cycle.

Four-dimensional (4D) flow magnetic resonance imaging (4D Flow MRI) enables acquisition of time-resolved three-directional velocity data in the entire heart and all major thoracic vessels. The segmentation of these tissues is typically performed using semi-automatic methods. Some of which primarily rely on the velocity data and result in a segmentation of the vessels only during the systolic phases. Other methods, mostly applied on the heart, rely on separately acquired balanced Steady State Free Precession (b-SSFP) MR images, after which the segmentations are superimposed on the 4D Flow MRI. While b-SSFP images typically cover the whole cardiac cycle and have good contrast, they suffer from a number of problems, such as large slice thickness, limited coverage of the cardiac anatomy, and being prone to displacement errors caused by respiratory motion. To address these limitations we propose a multi-atlas segmentation method, which relies only on 4D Flow MRI data, to automatically generate four-dimensional segmentations that include the entire thoracic cardiovascular system present in these datasets. The approach was evaluated on 4D Flow MR datasets from a cohort of 27 healthy volunteers and 83 patients with mildly impaired systolic left-ventricular function. Comparison of manual and automatic segmentations of the cardiac chambers at end-systolic and end-diastolic timeframes showed agreements comparable to those previously reported for automatic segmentation methods of b-SSFP MR images. Furthermore, automatic segmentation of the entire thoracic cardiovascular system improves visualization of 4D Flow MRI and facilitates computation of hemodynamic parameters.

Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. Methods: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at locations of interest. The method was applied on 4D flow CMR datasets obtained from 11 healthy volunteers and 10 patients with heart failure. Evaluation of the method was performed visually, and by comparison of net flow volumes in the ascending aorta obtained automatically (using the proposed method), and semi-automatically. Further evaluation was done by comparison of net flow volumes obtained automatically at different locations in the aorta, pulmonary artery, and caval veins. Results: Visual evaluation of the generated segmentations resulted in good outcomes for all the major vessels in all but one dataset. The comparison between automatically and semi-automatically obtained net flow volumes in the ascending aorta resulted in very high correlation (r(2) = 0.926). Moreover, comparison of the net flow volumes obtained automatically in other vessel locations also produced high correlations where expected: pulmonary trunk vs. proximal ascending aorta (r(2) = 0.955), pulmonary trunk vs. pulmonary branches (r(2) = 0.808), and pulmonary trunk vs. caval veins (r(2) = 0.906). Conclusions: The proposed method allows for automatic analysis of 4D flow CMR data, including vessel segmentation, assessment of flow volumes at locations of interest, and 4D flow visualization. This constitutes an important step towards facilitating the clinical utility of 4D flow CMR.

The fitness of firefighters is regularly evaluated using exercise tests. We aimed to compare, with respect to age and body composition, two test modalities for the assessment work capacity. A total of 424 Swedish firefighters with cycle ergometer (CE) and treadmill (TM) tests available from Jan 2004 to Dec 2010 were included. We compared results from CE (6 min at 200 W, 250 W or incremental ramp exercise) with TM (6 min at 8° inclination, 4·5 km h(-1) or faster, wearing 24-kg protective equipment). Oxygen requirements were estimated by prediction equations. It was more common to pass the TM test and fail the supposedly equivalent CE test (20%), than vice versa (0·5%), P<0·001. Low age and tall stature were significant predictors of passing both CE and TM tests (P<0·05), while low body mass predicted accomplishment of TM test only (P = 0·006). Firefighters who passed the TM but failed the supposedly equivalent CE test within 12 months had significantly lower body mass, lower BMI, lower BSA and shorter stature than did those who passed both tests. Calculated oxygen uptake was higher in TM tests compared with corresponding CE tests (P<0·001). Body constitution affected approval differently depending on the test modality. A higher approval rate in TM testing suggests lower cardiorespiratory requirements compared with CE testing, even though estimated oxygen uptake was higher during TM testing. The relevance of our findings in relation to the occupational demands needs reconsidering.

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics of pathophysiology that are otherwise difficult to obtain non-invasively in clinical practice.

Background-Biomarker activation in atrial fibrillation (AF) has been widely studied, but the immediate effect of AF initiation remains unclear. We studied the effect of AF initiation on 2 cardiac biomarkers: the N-terminal fragment of the proB-type natriuretic peptide (NT-proBNP), the midregional fragment of the N-terminal of pro-atrial natriuretic peptide (MR-proANP), and 2 extracardiac biomarkers-the copeptin and the midregional portion of proadrenomedullin (MR-proADM). Methods and Results-This was a randomized controlled study, including 45 patients with AF who had been referred for radiofrequency ablation to the University Hospital, Link_ oping, Sweden, between February 2012 and April 2014. Freedom from AF during the 4 days prior to radiofrequency ablation was confirmed by transtelephonic ECGs. Biomarkers were collected from the femoral vein (fv), coronary sinus (CS), and left atrium (LA) prior to AF initiation (baseline) and 30 minutes later. The MR-proANP and NT-proBNP concentrations increased in the intervention group compared with the control group 30 minutes after the initiation of AF (MR-proANP: P-fvamp;lt;0.001, P-CSamp;lt;0.001, P-LAamp;lt;0.001; NT-proBNP: P-LAamp;lt;0.001). Copeptin levels in patients without ischemic heart disease were decreased after the initiation of AF (P-fv= 0.003, P-CS= 0.015, P-LA= 0.011). Conclusions-AF is a strong stimulus that results in immediate activation of different biomarkers.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 1.5-2%. It is an independent risk factor for ischaemic stroke and is estimated to cause about 20-25% of all stroke cases. AF has a great impact on health-related quality of life (HRQoL); however, one unresolved issue related to AF is the wide variation in its symptoms.

METHODS AND ANALYSIS: The symptom burden, metabolic profile, ultrasound findings, rhythm, neurohormonal activation, haemodynamics and HRQoL in patients with AF (Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation, SMURF) study is a prospective observational, cohort study, with a randomised interventional part. The aim of the study is to investigate, in patients with AF, the relationship between symptom burden and metabolic aspects, atrial function and different neurohormones, and the effect of radiofrequency ablation (RFA). The interventional part of the study will give an insight into the neurohormonal and intracardiac pressure changes directly after initiation of AF. Consecutive patients with symptomatic AF accepted for treatment with RFA for the first time at Linköping University Hospital are eligible for participation. The enrolment started in January 2012, and a total of 200 patients are to be included into the study, with 45 of them being enrolled into the interventional study with initiation of AF. The sample size of the interventional study is based on a small pilot study with 5 patients induced to AF while 2 served as controls. The results indicated that, in order to find a statistically significant difference, there was a need to include 28 patients; for safety reasons, 45 patients will be included.

ETHICS AND DISSEMINATION: The SMURF study is approved by the Regional Ethical Review Board at the Faculty of Health Sciences, Linköping, Sweden. The results will be presented through peer-review journals and conference presentation.

Purpose: Hemodynamic atlases can add to the pathophysiological understanding of cardiac diseases. This study proposes a method to create hemodynamic atlases using 4D Flow magnetic resonance imaging (MRI). The method is demonstrated for kinetic energy (KE) and helicity density (Hd). Materials and Methods: Thirteen healthy subjects underwent 4D Flow MRI at 3T. Phase-contrast magnetic resonance cardioangiographies (PC-MRCAs) and an average heart were created and segmented. The PC-MRCAs, KE, and Hd were nonrigidly registered to the average heart to create atlases. The method was compared with 1) rigid, 2) affine registration of the PC-MRCAs, and 3) affine registration of segmentations. The peak and mean KE and Hd before and after registration were calculated to evaluate interpolation error due to nonrigid registration. Results: The segmentations deformed using nonrigid registration overlapped (median: 92.3%) more than rigid (23.1%, P amp;lt; 0.001), and affine registration of PC-MRCAs (38.5%, P amp;lt; 0.001) and affine registration of segmentations (61.5%, P amp;lt; 0.001). The peak KE was 4.9 mJ using the proposed method and affine registration of segmentations (P50.91), 3.5 mJ using rigid registration (P amp;lt; 0.001), and 4.2 mJ using affine registration of the PC-MRCAs (P amp;lt; 0.001). The mean KE was 1.1 mJ using the proposed method, 0.8 mJ using rigid registration (P amp;lt; 0.001), 0.9 mJ using affine registration of the PC-MRCAs (P amp;lt; 0.001), and 1.0 mJ using affine registration of segmentations (P50.028). The interpolation error was 5.262.6% at mid-systole, 2.863.8% at early diastole for peak KE; 9.669.3% at mid-systole, 4.064.6% at early diastole, and 4.964.6% at late diastole for peak Hd. The mean KE and Hd were not affected by interpolation. Conclusion: Hemodynamic atlases can be obtained with minimal user interaction using nonrigid registration of 4D Flow MRI. Level of Evidence: 2 Technical Efficacy: Stage 1

INTRODUCTION: We investigated if image- and diagnostic quality in SPECT MPI could be maintained despite a reduced acquisition time adding Depth Dependent Resolution Recovery (DDRR) for image reconstruction. Images were compared with filtered back projection (FBP) and iterative reconstruction using Ordered Subsets Expectation Maximization with (IRAC) and without (IRNC) attenuation correction (AC).

MATERIALS AND METHODS: Stress- and rest imaging for 15 min was performed on 21 subjects with a dual head gamma camera (Infinia Hawkeye; GE Healthcare), ECG-gating with 8 frames/cardiac cycle and a low-dose CT-scan. A 9 min acquisition was generated using five instead of eight gated frames and was reconstructed with DDRR, with (IRACRR) and without AC (IRNCRR) as well as with FBP. Three experienced nuclear medicine specialists visually assessed anonymized images according to eight criteria on a four point scale, three related to image quality and five to diagnostic confidence. Statistical analysis was performed using Visual Grading Regression (VGR).

RESULTS: Observer confidence in statements on image quality was highest for the images that were reconstructed using DDRR (P<0·01 compared to FBP). Iterative reconstruction without DDRR was not superior to FBP. Interobserver variability was significant for statements on image quality (P<0·05) but lower in the diagnostic statements on ischemia and scar. The confidence in assessing ischemia and scar was not different between the reconstruction techniques (P = n.s.).

CONCLUSION: SPECT MPI collected in 9 min, reconstructed with DDRR and AC, produced better image quality than the standard procedure. The observers expressed the highest diagnostic confidence in the DDRR reconstruction.

Background: Transcatheter aortic valve replacement (TAVR) has becomean established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. Methods and results: The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N = 154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30 days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30 days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth amp;lt;4 mm and a device/annulus ratio amp;lt; 1.05. Conclusions: The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND: The significance of a coronary stenosis can be determined by measuring the fractional flow reserve (FFR) during invasive coronary angiography. Recently, methods have been developed which claim to be able to estimate FFR using image data from standard coronary computed tomography angiography (CCTA) exams.

MATERIAL AND METHODS: A total of 23 vessels in 21 patients who had undergone both CCTA and invasive angiography with FFR measurement were evaluated using a cFFR software prototype. The cFFR results were compared to the invasively obtained FFR values. Correlation was calculated using Spearman's rank correlation, and agreement using intraclass correlation coefficient (ICC). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for significant stenosis (defined as both FFR ≤0.80 and FFR ≤0.75) were calculated.

RESULTS: The mean cFFR value for the whole group was 0.81 and the corresponding mean invFFR value was 0.84. The cFFR sensitivity for significant stenosis (FFR ≤0.80/0.75) on a per-lesion basis was 0.83/0.80, specificity was 0.76/0.89, and accuracy 0.78/0.87. The positive predictive value was 0.56/0.67 and the negative predictive value was 0.93/0.94. The Spearman rank correlation coefficient was ρ = 0.77 (P < 0.001) and ICC = 0.73 (P < 0.001).

CONCLUSION: This particular CCTA-based cFFR software prototype allows for a rapid, non-invasive on-site evaluation of cFFR. The results are encouraging and cFFR may in the future be of help in the triage to invasive coronary angiography.

INTRODUCTION: Myocardial dysfunction is a well-known complication in septic shock but its characteristics and frequency remains elusive. Here, we evaluate global longitudinal peak strain (GLPS) of the left ventricle as a diagnostic and prognostic tool in septic shock.

METHODS: Fifty adult patients with septic shock admitted to a general intensive care unit were included. Transthoracic echocardiography was performed on the first day, and repeated during and after ICU stay. Laboratory and clinical data and data on outcome were collected daily from admission and up to 7 days, shorter in cases of death or ICU discharge. The correlation of GLPS to left ventricular systolic and diastolic function parameters, cardiac biomarkers and clinical data were compared using Spearman's correlation test and linear regression analysis, and the ability of GLPS to predict outcome was evaluated using a logistic regression model.

RESULTS: On the day of admission, there was a strong correlation and co-linearity of GLPS to left ventricular ejection fraction (LVEF), mitral annular motion velocity (é) and to amino-terminal pro-brain natriuretic peptide (NT-proBNP) (Spearman's ρ -0.70, -0.53 and 0.54, and R(2) 0.49, 0.20 and 0.24, respectively). In LVEF and NT-proBNP there was a significant improvement during the study period (analysis of variance (ANOVA) with repeated measures, p = 0.05 and p < 0.001, respectively), but not in GLPS, which remained unchanged over time (p = 0.10). GLPS did not correlate to the improvement in clinical characteristics over time, did not differ significantly between survivors and non-survivors (-17.4 (-20.5-(-13.7)) vs. -14.7 (-19.0 - (-10.6)), p = 0.11), and could not predict mortality.

CONCLUSIONS: GLPS is frequently reduced in septic shock patients, alone or in combination with reduced LVEF and/or é. It correlates with LVEF, é and NT-proBNP, and remains affected over time. GLPS may provide further understanding on the character of myocardial dysfunction in septic shock.

BACKGROUND: Echocardiography is increasingly used for haemodynamic evaluation and titration of therapy in intensive care, warranting reliable and reproducible measurements. The aim of this study was to evaluate the observer dependence of echocardiographic findings of left ventricular (LV) diastolic and systolic dysfunction in patients with septic shock.

METHODS: Echocardiograms performed in 47 adult patients admitted with septic shock to a general intensive care unit (ICU) were independently evaluated by one cardiologist and one intensivist for the following signs: decreased diastolic tissue velocity of the base of the LV septum (e), increased early mitral inflow (E) to e ratio (E/e), decreased LV ejection fraction (EF) and decreased LV global longitudinal peak strain (GLPS). Diastolic dysfunction was defined as e <8.0cm/s and/or E/e [greater than or equal to]15 and systolic dysfunction as EF <50% and/or GLPS>15%. Ten randomly selected examinations were re-analysed two months later. Pearson’s r was used to test the correlation and Bland-Altman plots to assess the agreement between observers. Kappa statistics were used to test the consistency between readers and intraclass correlation coefficients (ICC) for inter- and intraobserver variability.

RESULTS: In 44 patients (94%), image quality was sufficient for echocardiographic measurements. The agreement between observers was moderate (k=0.60 for e, k=0.50 for E/e and k=0.60 for EF) to good (k=0.71 for GLPS). Pearson’s r was 0.76 for e, 0.85 for E/e, 0.78 for EF and 0.84 for GLPS (p<0.001 for all four). The ICC between observers for e was very good (0.85; 95% confidence interval (CI) 0.73-0.92), good for E/e (0.70; 95% CI 0.45 - 0.84), very good for EF (0.87; 95% CI 0.77 - 0.93), excellent for GLPS (0.91; 95% CI 0.74 - 0.95), and very good for all measures repeated by one of the observers. On Bland-Altman analysis, the mean differences and 95% limits of agreement for e, E/e, EF and GLPS were 0.01 (0.04 - 0.07), 2.0 (14.2 - 18.1), 0.86 (16 - 14.3) and 0.04 (5.04 - 5.12), respectively.

Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

Purpose: The purpose of this work was to assess the impact of respiratory motion and to compare methods for suppression of respiratory motion artifacts in 4D Flow MRI. Methods: A numerical 3D aorta phantom was designed based on an aorta velocity field obtained by computational fluid mechanics. Motion-distorted 4D Flow MRI measurements were simulated and several different motion-suppression techniques were evaluated: Gating with fixed acceptance window size, gating with different window sizes in inner and outer kspace, and k-space reordering. Additionally, different spatial resolutions were simulated. Results: Respiratory motion reduced the image quality. All motion-suppression techniques improved the data quality. Flow rate errors of up to 30% without gating could be reduced to less than 2.5% with the most successful motion suppression methods. Weighted gating and gating combined with kspace reordering were advantageous compared with conventional fixed-window gating. Spatial resolutions finer than the amount of accepted motion did not lead to improved results. Conclusion: Respiratory motion affects 4D Flow MRI data. Several different motion suppression techniques exist that are capable of reducing the errors associated with respiratory motion. Spatial resolutions finer than the degree of accepted respiratory motion do not result in improved data quality. (C) 2017 International Society for Magnetic Resonance in Medicine.

Purpose: To assess the spatial heterogeneity of the four-dimensional (4D) relative pressure fields in the healthy human left ventricle (LV) and provide reference data for normal LV relative pressure. Methods: Twelve healthy subjects underwent a cardiac MRI examination where 4D flow and morphological data were acquired. The latter data were segmented and used to define the borders of the LV for computation of relative pressure fields using the pressure Poisson equation. The LV lumen was divided into 17 pie-shaped segments. Results: In the normal left ventricle, the relative pressure in the apical segments was significantly higher relative to the basal segments (P &lt; 0.0005) along both the anteroseptal and inferolateral sides after the peaks of early (E-wave) and late (A-wave) diastolic filling. The basal anteroseptal segment showed significantly lower median pressure than the opposite basal inferolateral segment during both E-wave (P &lt; 0.0005) and A-wave (P = 0.0024). Conclusion: Relative pressure in the left ventricle is heterogeneous. During diastole, the main pressure differences in the LV occur along the basal-apical axis. However, pressure differences were also found in the short axis direction and may reflect important aspects of atrioventricular coupling. Additionally, this study provides reference data on LV pressure dynamics for a group of healthy subjects. (C) 2014 Wiley Periodicals, Inc.

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the anterior mitral valve leaflet (AML) is a known complication after mitral valve repair or transfemoral/transapical mitral valve implantation (TMVI). We present a patient with a previous mitral valve repair who developed LVOT obstruction after TMVI in whom the AML was surgically resected using a transaortic approach.

Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

Background: Physical activity is associated with health in women. Published MET-values (MET: metabolic equivalent of task) may assess physical activity and energy expenditure but tend to be too low for subjects with a high total body fat (TBF) content and therefore inappropriate for many contemporary women. The MET-value for an activity is the energy expenditure of a subject performing this activity divided by his/her resting energy expenditure, often assumed to be 4.2 kJ/kg/h. Relationships between TBF and MET have been little studied although overweight and obesity is common in women. Available data indicate that MET-values decrease during pregnancy but more studies in pregnant contemporary women are needed. Subjects and methods: Using indirect calorimetry we measured energy expenditure and assessed MET-values in women, 22 non-pregnant (BMI: 18-34) and 22 in gestational week 32 (non-pregnant BMI: 18-32) when resting, sitting, cycling (30 and 60 watts), walking (3.2 and 5.6 km/h) and running (8 km/h). Relationships between TBF and MET-values were investigated and used to predict modified MET-values. The potential of such values to improve calculations of total energy expenditure of women was investigated. Results: The resting energy expenditure was below 4.2 kJ/kg/h in both groups of women. Women in gestational week 32 had a higher resting energy metabolism (p amp;lt; 0.001) and 7-15% lower MET-values (p amp;lt; 0.05) than non-pregnant women. MET-values of all activities were correlated with TBF (p amp;lt; 0.05) in non-pregnant women and modified MET-values improved estimates of total energy expenditure in such women. In pregnant women, correlations (p amp;lt;= 0.03) between TBF and MET were found for running (8 km/h) and for walking at 5.6 km/h. Conclusions: Our results are relevant when attempts are made to modify the MET-system in contemporary pregnant and non-pregnant women. MET-values were decreased in gestational week 32, mainly due to an increased resting energy metabolism and studies describing how body composition affects the one MET-value (i.e. the resting energy metabolism in kJ/kg/h) during pregnancy are warranted. Studies of how pregnancy and TBF affect MET-values of high intensity activities are also needed. Corrections based on TBF may have a potential to improve the MET-system in non-pregnant women.

MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling.

Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair.

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinsons disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand I-123-FP-CIT (DaTSCAN (R)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

Background: Olfactory impairment is an early manifestation of Parkinsons disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.